Detection and analysis of low concentrations of analytes in various biologic and organic environments is becoming increasingly important. For a sensing approach to be useful not only for diagnosis, but also to monitor low levels of residual disease, the limits of detection must presently reach low levels, for example femtomolar levels, to achieve the detection of scarce analytes in clinical samples with an acceptably low level of false negatives. High levels of specificity are required to ensure low levels of false positives. From a practical perspective, equally important is a streamlined approach to sample workup, since the need for extensive sample processing can overwhelm the benefits of a sensor's innate high sensitivity and specificity.
Qualitative analysis is generally limited to the higher concentration levels, whereas quantitative analysis usually requires labeling with a radioisotope or fluorescent reagent. Such procedures are generally time consuming and inconvenient. Recent advances in developing bioelectronic biological marker analysis systems open up new opportunities for molecular diagnostics and have attracted substantial research efforts (Boon, E. M., et al., Nat. Biotechnol., 18, 1096, 2000; Rodriguez, M. & Bard, A., J. Anal. Chem., 62, 1658, 1990). Optical (Jordan, C. E., et al., Anal. Chem., 69, 4939, 1997; Fotin, A. V., et al., Nucleic Acids Res., 26, 1515, 1998), electrochemical (Kelley, S. O., et al., Bioconjug. Chem., 8, 31, 1997; Kelly, S. O., et al., Nucleic Acids Res., 27, 4830, 1999), and microgravimetric and quartz-crystal microbalance (Bardea, A., et al., Chem. Commun., 839, 1998; Wang, J., Nucleic Acids Res., 28, 3011, 2000), transduction methods have been reported for the detection of DNA hybridization events.
One of the objectives disclosed herein is to provide biomolecule based bioprobes that are free of aggregation. Another object is the use of the disclosed bioprobes useful to detect small quantities of biological markers. Another objective is to provide biosensors that comprise the bioprobes described herein. An additional objective is to provide biosensors that comprise the bioprobes described herein, immobilized on a suitable substrate, and a suitable reporter system attached thereto.